A high pathological complete response (pCR, 21%; pathologic response rate, 54%) was also observed with add-on letrozole (+ luteinizing hormone-releasing hormone [LHRH] agonist in pre-menopausal women) to a 12-week trastuzumab–lapatinib combination in patients with estrogen receptor (ER) positive (ER+) HER2+ breast cancer in a phase 2 study [12]. The gene discussed is ESR1; the disease is breast carcinoma.